Fusion proteins for the diagnosis, prophylaxis and treatment of infectious diseases

Abstract

The present invention inter alia relates to the use of phosphotidylserine or pathogenic sugar targeted therapeutics for the management and treatment of microbial infections, including Zika, Dengue, West Nile, Ebola, H1N1, enteroviruses, Leishmaniasis, Malaria and Coronaviruses SARS-COV. In an aspect, the invention concerns a fusion construct comprising an Ig-Fc domain or other protein scaffold, such as albumin, and a peptide, protein, or antibody fragment binding to phosphatidylserine and/or a peptide or protein binding to and/or recognizing a PAMP expressed by a microbe. Other aspects are described.

1 . A fusion construct comprising an Ig-Fc domain or other protein scaffold, such as albumin or an antibody fragment binding to albumin, and 
 a. a peptide, protein or antibody fragment binding to phosphatidylserine and/or   b. a peptide or protein binding to and/or recognizing a PAMP expressed by a microbe.   
     
     
         2 . A fusion construct, preferably according to  claim 1 , comprising an IgG-Fc domain or other protein scaffold and
 a. a recombinant human TIM1 fragment and/or   b. a recombinant human CD209 fragment.   
     
     
         3 . A fusion construct according to any of  claims 1-2 , comprising an IgG-Fc domain or other protein scaffold, and 
 a. A recombinant Ig-like V-type domain of a human TIM1 and/or   b. A recombinant C-type lectin domain of a human CD209 fragment.   
     
     
         4 . A fusion construct according to  claim 3 , comprising an IgG-Fc domain or other protein scaffold, and 
 a. Two or more recombinant Ig-like V-type domains from one or more human TIM1 and/or   b. Two or more recombinant C-type lectin domains from one or more human CD209 fragment(s).   
     
     
         5 . A fusion construct comprising
 a. A recombinant Ig-like V-type domain of a human TIM1 and   b. A recombinant C-type lectin domain of a human CD209 fragment.   
     
     
         6 . A fusion construct, preferably according to  any of the preceding claims  comprising an IgG-Fc domain or other protein scaffold and
 a. a recombinant human TIM1 fragment and/or 
 b. a recombinant human CD209 fragment 
and wherein said fusion construct provides enhanced ADCC, ADCP and/or CDC. 
     
     
         7 . A fusion construct, preferably according to  any of the preceding claims  comprising an IgG-Fc domain or other protein scaffold and
 a. a recombinant human TIM1 fragment and/or 
 b. a recombinant human CD209 fragment 
 and wherein said fusion construct additionally comprises the CDR regions according to SEQ ID No.: 54 - 59. 
     
     
         8 . A fusion construct, preferably according to  any of the preceding claims  comprising an IgG-Fc domain or other protein scaffold and
 a. a recombinant human TIM1 fragment and/or 
 b. a recombinant human CD209 fragment 
 and wherein said fusion construct further comprises a Furin inhibitor. 
     
     
         9 . The fusion construct according to  any of the preceding claims , wherein said peptide, protein or antibody fragment is capable of binding to and/or stimulating an immune cell. 
     
     
         10 . The fusion construct according to  any of the preceding claims , wherein said TIM1 fragment has a sequence length selected from the group consisting of 40-200 amino acid residues, 50-180 amino acid residues, 60-160 amino acid residues, 70-140 amino acid residues, 80-130 amino acid residues, 90-120 amino acid residues, 100-120 amino acid residues and 100-110 amino acid residues. 
     
     
         11 . The fusion construct according to  any of the preceding claims , wherein said CD209 fragment has a sequence length selected from the group consisting of 40-200 amino acid residues, 40-190 amino acid residues, 50-180 amino acid residues, 60-170 amino acid residues, 70-160 amino acid residues, 80-150 amino acid residues, 90-150 amino acid residues, 100-150 amino acid residues, 110-150 amino acid residues, 120-150 amino acid residues and 130-140 amino acid residues. 
     
     
         12 . The fusion construct according to  any of the preceding claims , wherein said TIM1 and/or CD209 fragment has a sequence homology of at least 70%, alternatively 75%, alternatively 80%, alternatively 85%, alternatively 90%, alternatively 95% to wildtype TIM1 or CD209. 
     
     
         13 . The fusion construct according to  any of the preceding claims , wherein said TIM1 and/or CD209 fragment has intact TIM1 and/or CD209 function. 
     
     
         14 . The fusion construct according to  any of the preceding claims , wherein said IgG-Fc domain is an IgG3-Fc domain. 
     
     
         15 . The fusion construct according to  any of the preceding claims , comprising additionally at least one of the following:
 a) An IgG3, wherein the hinge sequence has been replaced, preferably with an IgG4 or IgG1 hinge sequence;   b) CDR regions according to SEQ ID No.: 54 - 59; and/or   c) A furin inhibitor.   
     
     
         16 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises a sequence according to SEQ ID No.: 1 and/or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
     
     
         17 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises a sequence according to SEQ ID No.: 3 and/or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
     
     
         18 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7 or preferably at least 8 disulfide bonds. 
     
     
         19 . The fusion construct according to  any of the preceding claims , wherein said fusion construct is capable of binding to a target, and wherein said target is a mannan, a high-mannose containing structure, a fucan, a phospholipid phosphatidylserine and/or CD3. 
     
     
         20 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A protein fragment comprising or consisting of a sequence according to SEQ ID No.: 1, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to a sequence according to SEQ ID No.: 1, and   b. a protein fragment comprising or consisting of a sequence according to SEQ ID No.: 3 or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to a sequence according to SEQ ID No.: 3.   
     
     
         21 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences and 
 ii. a sequence according to SEQ ID No.: 9 or a sequence according to SEQ ID No.: 43,, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences and 
   b. A second chain comprising 
 iii. a sequence according to SEQ ID No.: 1or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iv. a sequence according to SEQ ID No.: 9 or a sequence according to SEQ ID No.: 43, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         22 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a sequence according to SEQ ID No.: 9 or a sequence according to SEQ ID No.: 43, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
   b. A second chain comprising 
 iii. a sequence according to SEQ ID SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iv. a sequence according to SEQ ID No.: 9 or a sequence according to SEQ ID No.: 43, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         23 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a sequence according to SEQ ID No.: 11 or a sequence according to SEQ ID No.: 45, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
   b. A second chain comprising
 iii. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iv. a sequence according to SEQ ID No.: 13 or a sequence according to SEQ ID No.: 47, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         24 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a sequence according to SEQ ID No.: 14 or 15, or SEQ ID No.: 66, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
   b. A second chain comprising 
 iii. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iv. a sequence according to SEQ ID No.: 16 or 17, or SEQ ID No.: 67, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences and 
 v. a linker sequence, preferably according to SEQ ID No.: 41, and 
 vi. a sequence according to any of the sequences selected among SEQ ID No.: 18 - 35, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         25 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a sequence according to SEQ ID No.: 14 or 15, or SEQ ID No.: 66, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
   b. A second chain comprising 
 iii. a sequence according to SEQ ID No.: 3 and/or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iv. a sequence according to SEQ ID No.: 16 or 17, or SEQ ID No.: 67, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences and 
 v. a linker sequence preferably according to SEQ ID No.: 41, and 
 vi. a sequence according to any of the sequences selected among SEQ ID No.: 18 - 35, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         26 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a sequence according to SEQ ID No.: 14 or 15, or SEQ ID No.: 66, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
   b. A second chain comprising 
 iii. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iv. a sequence according to SEQ ID No.: 16 or 17, or SEQ ID No.: 67, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 v. a linker sequence preferably according to SEQ ID No.: 41, and 
 vi. a sequence according to any of the sequences selected among SEQ ID No.: 18 - 35, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         27 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises 
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a sequence according to SEQ ID No.: 16 or 17, or SEQ ID No.: 67, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iii. a linker sequence preferably according to SEQ ID No.: 41, and 
 iv. a sequence according to any of the sequences selected among SEQ ID No.: 18 - 35, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
   b. A second chain comprising 
 v. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, 
 vi. a linker sequence preferably according to SEQ ID No.: 41, and 
 vii. a sequence according SEQ ID No.: 14 or 15, or SEQ ID No.: 66, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         28 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises a linker. 
     
     
         29 . The fusion construct according to  any of the preceding claims , wherein said linker is selected among a (GGGGS)3 linker (SEQ ID NO. 41), a (GGGGS)4 linker (SEQ ID NO. 70), a (GGGGS)5 linker (SEQ ID NO. 71) and a (GGGGS)6 linker (SEQ ID NO. 72). 
     
     
         30 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises at least one free cysteine residue, at least two free cysteine residues, at least three free cysteine residues, at least four free cysteine residues, at least five free cysteine residues or preferably at least six free cysteine residues. 
     
     
         31 . The fusion construct according to  any of the preceding claims , wherein said free cysteine allows interaction with a drug and/or a payload. 
     
     
         32 . The fusion construct according to  any of the preceding claims , wherein said payload is a furin inhibitor. 
     
     
         33 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises a A339C mutation, a S337C mutation and/or a K340C mutation. 
     
     
         34 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises a sequence selected among any of the sequences SEQ ID No.: 36, 37, SEQ ID No.: 38, 39, 40, 42, 44 or 46. 
     
     
         35 . The fusion construct according to  any of the preceding claims , wherein said fusion construct is an IgG1, IgG2, IgG3 or an IgG4. 
     
     
         36 . The fusion construct according to  any of the preceding claims , wherein said fusion construct is an IgG, IgM, IgA, IgD or an IgE. 
     
     
         37 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises a null fc. 
     
     
         38 . The fusion construct according to  any of the preceding claims , wherein said null fc comprises an Ala substitution at position 234 and/or Ala substitution at 235, and/or N297A, and/or a K322A mutation. 
     
     
         39 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises a heterodimerization domain. 
     
     
         40 . The fusion construct according to  any of the preceding claims , wherein said heterodimerization domain comprises a sequence according to SEQ ID No.: 48, 49 or 50. 
     
     
         41 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises a heterodimerization mutation. 
     
     
         42 . The fusion construct according to  any of the preceding claims , wherein said heterodimerization mutation is an F405L, R409K and/or K409R mutation. 
     
     
         43 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a sequence according to SEQ ID No.: 38, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to this sequence, and 
   b. A second chain comprising 
 iii. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iv. a sequence according to SEQ ID No.: 38, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to this sequence. 
   
     
     
         44 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a sequence according to SEQ ID No.: 38, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
   b. A second chain comprising 
 iii. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iv. a sequence according to SEQ ID No.: 38, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         45 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising 
 i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a sequence according to SEQ ID No.: 38, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
   b. A second chain comprising 
 iii. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 iv. a sequence according to SEQ ID No.: 40, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         46 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising
 i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a linker sequence according to SEQ ID No.: 41, and 
 iii. a sequence according to SEQ ID No.: 65, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences 
   b. A second chain comprising
 iv. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 v. a linker sequence according to SEQ ID No.: 41, and 
 vi. a sequence according to SEQ ID No.: 65, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         47 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising
 i. a sequence according to SEQ ID No.: 3 or SEQ ID No.:4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a linker sequence according to SEQ ID No.: 41, and 
 iii. a sequence according to SEQ ID No.: 65, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences 
   b. A second chain comprising
 iv. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 v. a linker sequence according to SEQ ID No.: 41, and 
 vi. a sequence according to SEQ ID No.: 65, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences. 
   
     
     
         48 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises:
 a. A first chain comprising
 i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 ii. a linker sequence according to SEQ ID No.: 41, and 
 iii. a sequence according to SEQ ID No.: 65, wherein said sequence ID No.: 65 comprises one or more of the mutations of table 8 
   b. A second chain comprising 
 iv. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, or a sequence with at least 90% sequence identity, preferably at least 95% sequence identity, more preferred at least 98% sequence identity to one of these sequences, and 
 v. a linker sequence according to SEQ ID No.: 41, and 
 vi. a sequence according to SEQ ID No.: 65, wherein said sequence ID No.: 65 comprises one or more of the mutations of table 8. 
   
     
     
         49 . The fusion construct according to  any of the preceding claims , wherein the ratio of fusion construct to said drug and/or payload is selected among 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. 
     
     
         50 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises a kappa light chain according to SEQ ID No.: 51 or a lambda light chain according to SEQ ID No.: 52 or 53. 
     
     
         51 . A fusion construct, preferably according to  any of the preceding claims , wherein said fusion construct is an IgG3 construct, and wherein said IgG3 construct comprises a hinge region, wherein said hinge region has been modified. 
     
     
         52 . The fusion construct according to  claim 51 , wherein said hinge region comprises a sequence having a total of at least 10% identity, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identity to the sequence according to SEQ ID No.: 6 or SEQ ID No.: 8. 
     
     
         53 . The fusion construct according to  any of the preceding claims , wherein said fusion construct comprises the sequence according to SEQ ID No.: 5, 7, 9, 10, 11, 12 and/or 13. 
     
     
         54 . The fusion construct according to  any of the preceding claims , wherein said hinge region comprises at least one free cysteine residue, at least two free cysteine residues or preferably at least three free cysteine residues. 
     
     
         55 . The fusion construct according to  any of the preceding claims , wherein said hinge region comprises a S228P mutation. 
     
     
         56 . The fusion construct according to  any of the preceding claims , wherein said hinge region comprises a sequence according to SEQ ID No.: 6 and/or SEQ ID No.: 8 and/or SEQ ID No.: 68. 
     
     
         57 . The fusion construct according to  any of the preceding claims , wherein said fusion construct is used to detect phosphatidylserine. 
     
     
         58 . The fusion construct according to  any of the preceding claims , wherein said fusion construct is used to detect phosphatidylserine in the blood of a subject. 
     
     
         59 . The fusion construct according to  claim 57 , wherein said fusion construct comprises a sequence according to SEQ ID No.: 1, and/or a sequence according to SEQ ID No.: 2. 
     
     
         60 . The fusion construct according to  any of the preceding claims , wherein said fusion construct is used to detect C-type lectin binding mannan or fucan moieties. 
     
     
         61 . The fusion construct according to  any of the preceding claims , wherein said fusion construct is used to detect C-type lectin binding mannan or fucan moieties in the blood of a subject. 
     
     
         62 . The fusion construct according to  claim 60 , wherein said fusion construct comprises a sequence according to SEQ ID No.: 3 and/or a sequence according to SEQ ID No.: 4. 
     
     
         63 . A fusion construct, a fusion protein or an antibody comprising the constant region(s) of IgG3 and a hinge, wherein said hinge preferably is selected among an IgG1 or IgG4 hinge. 
     
     
         64 . The fusion construct, fusion protein or antibody according to any  claim 63 , comprising one or more heterodimerization mutations. 
     
     
         65 . The fusion construct, fusion protein or antibody according to  claim 64 , comprising heterodimerization mutations involving or including positions 405 and/or 409 (EU numbering). 
     
     
         66 . IgG3 homodimer comprising a hinge region, wherein said hinge region comprises a sequence selected among SEQ ID No.: 6, 8 and 68. 
     
     
         67 . IgG3 heterodimer comprising a hinge region, wherein said hinge region comprises a sequence selected among SEQ ID No.: 6, 8 and 68. 
     
     
         68 . IgG3 according to any of  claims 66-67 , wherein said IgG3 comprises a mutation at position 405 and/or position 409. 
     
     
         69 . IgM heterodimers obtainable by changing the charge pairs of the CH2 and/or CH4 domains. 
     
     
         70 . IgM heterodimers according to  claim 69 , comprising one or more of the mutations of Table 8. 
     
     
         71 . The IgM according to any  claims 69-70 , wherein said IgM comprises a sequence according to SEQ ID No.: 64 and/or 65. 
     
     
         72 . A fusion construct according to any of  claims 1-65 , wherein said fusion construct comprises an IgG3 homodimer, an IgG3 heterodimer and/or an IgM heterodimer according to any of  claims 66-71 . 
     
     
         73 . The fusion construct according to  any of the preceding claims , wherein said fusion construct is for use in the treatment of an infection. 
     
     
         74 . The fusion construct according to  claim 73 , wherein said infection is an infection caused by a virus, such as Coronaviruses SARS-COV, a parasite, a bacteria, a fungi or a protozoan. 
     
     
         75 . The fusion construct according to  claims 74 , wherein said virus is selected among an arborvirus, Zika virus, Dengue virus, West Nile virus, Ebola virus, influenza virus, influenza virus H1N1, Chikungunya virus, enterovirus, Coronavirus SARS-COV-2 and Coronaviruses SARS-COV. 
     
     
         76 . The fusion construct according to  claim 74 , wherein said bacteria is selected among mycobacterium tuberculosis and mycobacterium leprae. 
     
     
         77 . The fusion construct according to  claim 74 , wherein said parasite is selected among Leishmaniasis and Malaria. 
     
     
         78 . Use of a fusion construct according to any of  claims 1-71 , for the treatment of an infection. 
     
     
         79 . Use according to  claim 78 , wherein said infections are selected among viral, bacterial and protozoan infections. 
     
     
         80 . Use according to any  claims 78-79 , wherein the treatment comprising administration of the fusion construct with an administration form selected among subcutaneous, intradermal, intramuscular, oral and nasal. 
     
     
         81 . Use of IgG4 or a part of IgG4 for payload delivery, wherein said IgG4 has been modified to comprise no Fc or wherein the activity of the Fc of said IgG4 has been nullified or diminished by one or more mutations. 
     
     
         82 . The use according to any of  claims 78-81 , wherein said IgG4 comprises one or more heterodimerization mutations. 
     
     
         83 . The use according to any of  claims 81-82 , wherein said IgG4 comprises one or more Cys mutations, preferably thereby allowing site specific conjugation. 
     
     
         84 . The use according to any of  claims 81-83 , wherein said IgG4 comprises a Cys at position 339 (EU numbering). 
     
     
         85 . A vaccine comprising a fusion construct according to any of  claims 1-65 . 
     
     
         86 . A vaccine comprising a mannan, a high mannose containing structure, a fucan and/or a phospholipid phosphatidylserine (PS). 
     
     
         87 . The vaccine according to  claim 85  or  86 , further comprising β-glucan. 
     
     
         88 . The vaccine according to any of  claims 85-87 , for the prevention and/or treatment of an infection. 
     
     
         89 . The vaccine according to  claim 88 , wherein said infection is caused by a virus, preferably according to  claim 75 , and/or Coronaviruses SARS-COV, a parasite, preferably according to  claim 77 , a bacteria, preferably according to  claim 76 , a fungi or a protozoan. 
     
     
         90 . The fusion construct according to any of  claims 1-65  and/or vaccine according to any of  claims 85-89 , wherein said fusion construct and/or vaccine allows administration through a route selected among subcutaneous administration, intradermal administration, intramuscular administration, oral administration and/or nasal administration. 
     
     
         91 . A composition comprising a fusion construct according to any of  claims 1-65 , optionally comprising one or more excipients such as diluents, binders or carriers. 
     
     
         92 . A method of treating and/or preventing an infection in a subject, comprising a step of administration of a fusion construct according to any of  claims 1-65  and/or a vaccine according to any of  claims 85-89  and/or a composition according to any of  claims 90-91 . 
     
     
         93 . A method of screening and/or monitoring progression of a disease in a subject, wherein said method comprises the following steps:
 i. Providing a blood sample from said subject.   ii. Contacting said blood sample with a fusion construct according to any of  claims 1-65 .   
     
     
         94 . An isolated nucleic acid molecule encoding a fusion construct according to any of  claims 1-65 . 
     
     
         95 . A recombinant vector comprising the nucleic acid molecule of  claim 94 . 
     
     
         96 . A host cell comprising the recombinant vector of  claim 95 . 
     
     
         97 . A method for the production of a fusion construct according to  any of the precedent claims  comprising a step of culturing the host cell according to  claim 96  in a culture medium under conditions allowing the expression of the fusion construct and separating the fusion construct from the culture medium.